Quantifying the Role of Regional Dyssynchrony on Global Left Ventricular Performance

Abstract

We hypothesize that left ventricular (LV) segmental dyssynchrony, quantified by paradoxical systolic wall thinning, determines changes in global LV performance in a model of canine right ventricular (RV) pacing-induced dyssynchrony and the response to cardiac resynchronization therapy (CRT). Quantification of LV dyssynchrony is important to assess the impact of CRT. Seven pentobarbital-anesthetized open-chest dogs had LV pressure-volume relations and mid-LV short-axis echocardiographic speckle tracking radial strain imaging during right atrial (RA) pacing, RV pacing to simulate left bundle branch block, and CRT using RV pacing plus either LV free-wall (CRTfw) and apical (CRTa) pacing. The area under the segmental LV time-radial strain positive and negative curves defined global thickening and thinning, respectively. Dyssynchrony was defined as the maximum time difference between earliest and latest peak segmental positive strain among 6 radial sites. RA pacing had minimal dyssynchrony (58 + or - 40 ms). RV pacing induced both dyssynchrony (213 + or - 67 ms, p < 0.05) and reduced LV stroke work (SW) (67 + or - 51 mJ, p < 0.05). CRTfw and CRTa decreased dyssynchrony (116 + or - 47 ms and 50 + or - 34 ms, respectively, p < 0.05 vs. RV pacing), but only CRTa restored LV SW to RA pacing levels. RV pacing decreased global thickening (129 + or - 87%.ms) compared with RA pacing (258 + or - 133%.ms, p < 0.05), whereas CRTfw and CRTa restored regional thickening to RA pacing levels (194 + or - 83%.ms and 230 + or - 76%.ms, respectively). The sum of thickening and thinning during RV (230 + or - 88%.ms vs. 258 + or - 133%.ms, p < 0.05) correlated (r = 0.98) with RA thickening, suggesting that all the loss of LV function was due to thinning. Dyssynchrony causes proportional changes in regional LV wall thinning and global LV SW that were reversed by CRT, suggesting that dyssynchrony impairs LV systolic function by causing paradoxical regional wall thinning and that CRT effectiveness can be monitored by its reversal. Thus, monitoring paradoxical regional thinning reversal may be used to define CRT effectiveness.